Long-term Safety and Tolerability of Idalopirdine (Lu AE58054) as Adjunctive Treatment to Donepezil in Patients With Mild-moderate Alzheimer's Disease
- Registration Number
- NCT02079246
- Lead Sponsor
- H. Lundbeck A/S
- Brief Summary
To evaluate the long-term safety and tolerability of idalopirdine (Lu AE58054) as adjunctive therapy to donepezil in patients with mild-moderate Alzheimer's Disease (AD).
- Detailed Description
This is an interventional, multi-national, multi-site, open-label extension study in patients with mild to moderate AD who completed the 24-week lead-in study 14861A (NCT01955161) or 14862A (NCT02006641).
Patients received 28-weeks of open-label treatment with idalopirdine 60 mg/day (option to reduce to 30 mg/day) as adjunctive treatment to donepezil. Approximately 100 patients, who had completed the initial 28-week period (OLEX), were included in a 24 week open-label treatment period with memantine (OLEX-MEM) that evaluated the safety and tolerability of concomitant memantine therapy in patients who were already on a stable treatment with idalopirdine and donepezil and for whom memantine treatment was clinically indicated.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1463
- the patient has completed Visit 7 (Completion Visit) in the lead-in double-blind, placebo controlled clinical studies 14861A/NCT01955161 or 14862A/NCT02006641
For patients in the OLEX-MEM:
- The patient has completed Visit 6 (Week 28) of the OLEX.
- The patient, according to the judgement of the investigator, requires initiation of treatment with memantine as per local label/SmPC/treatment guidelines.
- The patient has a moderate or severe ongoing adverse event from the lead-in study considered a potential safety risk by the investigator.
- The patient has experienced seizures before Completion Visit in the lead-in study.
- The patient has evidence of clinically significant disease.
- The patient's donepezil treatment is likely to be interrupted or discontinued during the study.
- The patient is receiving therapy with another acetylcholinesterase inhibitors (AChEI).
Other protocol-defined inclusion and exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Idalopirdine 60 mg + memantine Idalopirdine 60 mg Idalopirdine 60 mg as adjunct to 10 mg donepezil and memantine (patient's individualised maintenance dose, either immediate-release (IR) 20 mg/day (recommended target dose) or extended release (XR) 28 mg/day (recommended target dose). Memantine was administered to approximately 100 patients included in the OLEX-MEM. The dose of idalopirdine could be decreased from 60 mg to 30 mg if 60 mg was not well tolerated. The dose of donepezil was to be maintained throughout the study. The dose of memantine could be changed at any time throughout the study. Idalopirdine (Lu AE58054) 60 mg Idalopirdine 60 mg Idalopirdine 60 mg adjunct to 10 mg donepezil. The dose of idalopirdine could be decreased from 60 mg to 30 mg if 60 mg was not well tolerated. The dose of donepezil was to be maintained throughout the study.
- Primary Outcome Measures
Name Time Method Number of Treatment Emergent Adverse Events (TEAEs) in the OLEX Baseline II (start of OLEX, week 0) to end of OLEX (week 28) A TEAE is an adverse event that starts or increases in intensity after the date of Baseline II.
Number of TEAEs in the OLEX-MEM From Baseline III (start of OLEX-MEM, Week 28) to end of OLEX-MEM (Week 52) A TEAE is an adverse event that starts or increases in intensity after the date of Baseline III (start of OLEX-MEM).
- Secondary Outcome Measures
Name Time Method Change in Cognitive Aspects of Mental Function Baseline III (start of OLEX-MEM, Week 28) to Week 52 Change from Baseline III to Week 52 in Mini Mental State Examination (MMSE). The MMSE is an 11-item test to assess the cognitive aspects of mental function. The subtests assess orientation, memory, attention, language, and visual construction. The scores for each item is dichotomous (1 = response is correct, 0 = response is incorrect). Total score of the 11 items ranges from 0 to 30 (higher score indicates lower deficit).
Change in Cognition Baseline II (start of OLEX, Week 0) to Week 28 Change from Baseline II to Week 28 in Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog) total score. The ADAS-cog is a 11-item neuropsychological test that assess the severity of cognitive impairment. The items determine the patient's orientation, memory, language, and praxis. Total score of the 11 items range from 0 to 70 (lower score indicates lower cognitive impairment).
Change in Behavioural Disturbance Baseline II (start of OLEX, Week 0) to Week 28 Change from Baseline II to Week 28 in Neuropsychiatric Inventory (NPI) total score. The NPI is a 12-item structured interview with a caregiver to assess behavioural disturbances. The NPI comprises 10 behavioural and 2 neurovegetative items. Each item consists of a screening question and several sub-questions that are rated no (not present) or yes (present). Each item is rated for frequency (a 4-point scale from 1 \[occasionally\] to 4 \[very frequent\]) and severity (a 3-point scale from 1 \[mild\] to 3 \[marked\]). The total NPI score is the frequency ratings multiplied by the severity ratings and ranges from 0 to 144 (higher score indicates worse outcome).
Clinical Global Impression Score Week 28 Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) score at Week 28. The ADCS-CGIC is a semi-structured interview to assess clinically relevant changes in patients with AD. The items determine cognition, behavior, social and daily functioning. Severity at baseline is rated on a 7-point scale from 1 (normal, not ill at all) to 7 (among the most extremely ill patients). The clinically relevant change from baseline is rated on a 7-point scale from 1 (marked improvement) to 7 (marked worsening).
Change in Daily Functioning Baseline II (start of OLEX, Week 0) to Week 28 Change from Baseline II to Week 28 in Alzheimer's Disease Cooperative Study - Activities of Daily Living Inventory (ADCS-ADL23) total score. The ADCS-ADL23 is a 23-item clinician-rated inventory to assess activities of daily living (conducted with a caregiver or informant). Each item comprises a series of hierarchical sub-questions, ranging from the highest level of independent performance to a complete loss for each activity. Total score of the 23 items ranges from 0 to 78 (higher score indicates lower disability).
Trial Locations
- Locations (258)
US346
🇺🇸Costa Mesa, California, United States
US310
🇺🇸Saint Paul, Minnesota, United States
US024
🇺🇸Little Rock, Arkansas, United States
FR003
🇫🇷Nantes Cedex, France
US050
🇺🇸Brooksville, Florida, United States
US320
🇺🇸Hallandale Beach, Florida, United States
US356
🇺🇸Cordova, Tennessee, United States
US340
🇺🇸Lake Worth, Florida, United States
US308
🇺🇸Delray Beach, Florida, United States
US035
🇺🇸Kalamazoo, Michigan, United States
US046
🇺🇸Princeton, New Jersey, United States
US038
🇺🇸Port Charlotte, Florida, United States
US321
🇺🇸Hattiesburg, Mississippi, United States
US041
🇺🇸Flowood, Mississippi, United States
US345
🇺🇸Orange City, Florida, United States
US309
🇺🇸Palm Beach Gardens, Florida, United States
AR005
🇦🇷Mendoza, Argentina
US036
🇺🇸Freeport, Maine, United States
US302
🇺🇸Sunrise, Florida, United States
US319
🇺🇸Port Royal, South Carolina, United States
US334
🇺🇸Lake Charles, Louisiana, United States
US339
🇺🇸Manchester, New Jersey, United States
AR303
🇦🇷Banfield, Argentina
AR004
🇦🇷Mar del Plata, Argentina
AR310
🇦🇷Mendoza, Argentina
AR010
🇦🇷Rosario, Argentina
BE005
🇧🇪Leuven, Belgium
BE001
🇧🇪Roeselare, Belgium
BR307
🇧🇷Curitiba, Brazil
AR314
🇦🇷Ciudad Autonoma Buenos Aires, Argentina
AR312
🇦🇷Ciudad Autonoma de Buenos Aires, Argentina
AR009
🇦🇷Cordoba, Argentina
US028
🇺🇸Toms River, New Jersey, United States
AR007
🇦🇷Buenos Aires, Argentina
AR304
🇦🇷Ciudad Autonoma Buenos Aires, Argentina
AR311
🇦🇷Ciudad Autonoma Buenos Aires, Argentina
AR313
🇦🇷Ciudad Autonoma Buenos Aires, Argentina
AR309
🇦🇷Cordoba, Argentina
AR305
🇦🇷Godoy Cruz, Argentina
AR008
🇦🇷Mendoza, Argentina
AR302
🇦🇷Santa Fe, Argentina
AR306
🇦🇷Santiago del Estero, Argentina
BE003
🇧🇪Brugge, Belgium
BR309
🇧🇷Curitiba, Brazil
BR303
🇧🇷Porto Alegre, Brazil
BR301
🇧🇷Rio de Janeiro, Brazil
BR306
🇧🇷Rio de Janeiro, Brazil
BR304
🇧🇷São Paulo, Brazil
BG006
🇧🇬Sofia, Bulgaria
CA002
🇨🇦Gatineau, Canada
CA309
🇨🇦Gatineau, Canada
CA301
🇨🇦Halifax, Canada
CA302
🇨🇦Kelowna, Canada
CA006
🇨🇦London, Canada
BR302
🇧🇷Sao Paulo, Brazil
BR308
🇧🇷São Paulo, Brazil
BG005
🇧🇬Plovdiv, Bulgaria
BG001
🇧🇬Sofia, Bulgaria
BG002
🇧🇬Sofia, Bulgaria
BG003
🇧🇬Sofia, Bulgaria
BG004
🇧🇬Sofia, Bulgaria
CA306
🇨🇦Montreal, Canada
CA008
🇨🇦Newmarket, Canada
CA304
🇨🇦Qubec, Canada
CA001
🇨🇦Toronto, Canada
CA305
🇨🇦Toronto, Canada
CA308
🇨🇦Toronto, Canada
CA307
🇨🇦Verdun, Canada
CL004
🇨🇱Antofagasta, Chile
CL002
🇨🇱Santiago, Chile
CL003
🇨🇱Santiago, Chile
CL005
🇨🇱Santiago, Chile
CL001
🇨🇱Valdivia, Chile
HR304
🇭🇷Zabok, Croatia
HR301
🇭🇷Zagreb, Croatia
HR302
🇭🇷Zagreb, Croatia
FI302
🇫🇮Kuopio, Finland
FR301
🇫🇷Bordeaux, France
FR308
🇫🇷Bron cedex, France
FR302
🇫🇷Marseille cedex 5, France
FR312
🇫🇷Nantes, France
FR311
🇫🇷Paris, France
FR305
🇫🇷Rouen, France
FR004
🇫🇷Saint Priest en Jarez, France
FR313
🇫🇷Saint Priest en Jarez, France
FR002
🇫🇷Toulouse, France
DE002
🇩🇪Berlin, Germany
DE006
🇩🇪Ellwangen, Germany
DE005
🇩🇪Hannover, Germany
DE007
🇩🇪Heidelberg, Germany
DE004
🇩🇪Unterhaching, Germany
HU304
🇭🇺Budapest, Hungary
HU301
🇭🇺Esztergom, Hungary
HU305
🇭🇺Budapest, Hungary
HU302
🇭🇺Szeged, Hungary
IL302
🇮🇱Haifa, Israel
IL303
🇮🇱Holon, Israel
IL304
🇮🇱Ramat Gan, Israel
IT004
🇮🇹Ancona, Italy
IT006
🇮🇹Brescia, Italy
IT306
🇮🇹Brescia, Italy
IT309
🇮🇹Brescia, Italy
IT313
🇮🇹Cefalù, Italy
IT311
🇮🇹Genova, Italy
IT001
🇮🇹Milano, Italy
IT312
🇮🇹Monza, Italy
IT007
🇮🇹Palermo, Italy
IT307
🇮🇹Perugia, Italy
IT301
🇮🇹Pisa, Italy
IT305
🇮🇹Roma, Italy
IT308
🇮🇹Roma, Italy
IT310
🇮🇹Torrette, Italy
KR301
🇰🇷Incheon, Korea, Republic of
KR302
🇰🇷Seoul, Korea, Republic of
KR304
🇰🇷Seoul, Korea, Republic of
KR305
🇰🇷Seoul, Korea, Republic of
KR306
🇰🇷Seoul, Korea, Republic of
LT301
🇱🇹Vilnius, Lithuania
KR309
🇰🇷Seoul, Korea, Republic of
PL004
🇵🇱Gliwice, Poland
PL005
🇵🇱Pozna, Poland
PL006
🇵🇱Sopot, Poland
PT301
🇵🇹Amadora, Portugal
RO002
🇷🇴Bucharest, Romania
RO001
🇷🇴Târgu-Mureş, Romania
CZ309
🇨🇿Chocen, Czechia
CZ306
🇨🇿Hradec Kralove, Czechia
CZ001
🇨🇿Praha 2, Czechia
CZ310
🇨🇿Praha 10 - Strasnice, Czechia
US307
🇺🇸Redlands, California, United States
US023
🇺🇸Imperial, California, United States
US030
🇺🇸Chicago, Illinois, United States
US301
🇺🇸Santa Rosa, California, United States
AR307
🇦🇷Cordoba, Argentina
US324
🇺🇸Pittsburgh, Pennsylvania, United States
US007
🇺🇸Centerville, Ohio, United States
US029
🇺🇸New York, New York, United States
US057
🇺🇸Jenkintown, Pennsylvania, United States
US347
🇺🇸Hialeah, Florida, United States
US312
🇺🇸Staten Island, New York, United States
US306
🇺🇸Columbus, Ohio, United States
CZ006
🇨🇿Brno, Czechia
US021
🇺🇸Bradenton, Florida, United States
US341
🇺🇸Pittsburgh, Pennsylvania, United States
AR003
🇦🇷Ciudad Autonoma Buenos Aires, Argentina
BE002
🇧🇪Brussels, Belgium
BE004
🇧🇪Bruxelles, Belgium
CZ007
🇨🇿Kutna Hora, Czechia
FR006
🇫🇷Besancon Cedex, France
FR005
🇫🇷Paris cedex 10, France
CZ003
🇨🇿Praha 10, Czechia
CZ304
🇨🇿Praha 10, Czechia
CZ004
🇨🇿Pardubice, Czechia
CZ005
🇨🇿Rychnov nad Kneznou, Czechia
FI303
🇫🇮Oulu, Finland
FI301
🇫🇮Turku, Finland
CZ002
🇨🇿Praha 6, Czechia
CZ303
🇨🇿Praha 6, Czechia
EE302
🇪🇪Tartu, Estonia
FR309
🇫🇷Elancourt, France
DK003
🇩🇰Aarhus N, Denmark
CZ301
🇨🇿Praha 6, Czechia
DE009
🇩🇪Munchen, Germany
DE008
🇩🇪Ulm, Germany
IT002
🇮🇹Firenze, Italy
IT003
🇮🇹Lamezia Terme, Italy
IT005
🇮🇹Palermo, Italy
IT304
🇮🇹Torino, Italy
KR303
🇰🇷Busan, Korea, Republic of
LT302
🇱🇹Kaunas, Lithuania
PL306
🇵🇱Lublin, Poland
PL307
🇵🇱Oswiecim, Poland
GB301
🇬🇧Glasgow, United Kingdom
ZA003
🇿🇦Bloemfontein, South Africa
PL310
🇵🇱Lubin, Poland
PL311
🇵🇱Szczecin, Poland
UA005
🇺🇦Kyiv, Ukraine
ZA001
🇿🇦Pretoria, South Africa
UA006
🇺🇦Kherson, Ukraine
UA001
🇺🇦Lviv, Ukraine
ZA007
🇿🇦Cape Town, South Africa
ZA004
🇿🇦George, South Africa
GB303
🇬🇧London, United Kingdom
UA007
🇺🇦Kyiv, Ukraine
GB307
🇬🇧Amersham, United Kingdom
ES001
🇪🇸San Sebastian, Spain
ES005
🇪🇸Manresa, Spain
GB302
🇬🇧Swindon, United Kingdom
GB308
🇬🇧London, United Kingdom
GB310
🇬🇧London, United Kingdom
US045
🇺🇸Long Beach, California, United States
US351
🇺🇸Carlsbad, California, United States
US304
🇺🇸Atlanta, Georgia, United States
US360
🇺🇸Augusta, Georgia, United States
US014
🇺🇸Manhasset, New York, United States
US006
🇺🇸Columbus, Ohio, United States
US316
🇺🇸Charlotte, North Carolina, United States
US048
🇺🇸Kailua, Hawaii, United States
DK001
🇩🇰Copenhagen, Denmark
US027
🇺🇸Birmingham, Alabama, United States
US012
🇺🇸Phoenix, Arizona, United States
US338
🇺🇸Phoenix, Arizona, United States
US058
🇺🇸San Francisco, California, United States
US303
🇺🇸Miami, Florida, United States
US313
🇺🇸Miami, Florida, United States
US040
🇺🇸Indianapolis, Indiana, United States
US323
🇺🇸Cincinnati, Ohio, United States
US333
🇺🇸Oklahoma City, Oklahoma, United States
US354
🇺🇸Houston, Texas, United States
GB306
🇬🇧Plymouth, United Kingdom
GB311
🇬🇧Plymouth, United Kingdom
GB309
🇬🇧Prescot, United Kingdom
GB304
🇬🇧Southampton, United Kingdom
PL302
🇵🇱Lodz, Poland
PL008
🇵🇱Wroclaw, Poland
US327
🇺🇸Fullerton, California, United States
US018
🇺🇸Santa Ana, California, United States
US344
🇺🇸Boston, Massachusetts, United States
US044
🇺🇸Toms River, New Jersey, United States
US352
🇺🇸Lakewood, Ohio, United States
US026
🇺🇸Portland, Oregon, United States
US343
🇺🇸Fort Worth, Texas, United States
US047
🇺🇸Arlington, Virginia, United States
US025
🇺🇸Madison, Wisconsin, United States
AR308
🇦🇷Ciudad Autonoma Buenos Aires, Argentina
EE303
🇪🇪Tallin, Estonia
EE301
🇪🇪Tallinn, Estonia
FR008
🇫🇷Limoges, France
FR303
🇫🇷Nice, France
FR001
🇫🇷Paris, France
FR306
🇫🇷Reims, France
KR308
🇰🇷Seongnam-si, Korea, Republic of
KR307
🇰🇷Seoul, Korea, Republic of
LT304
🇱🇹Vilnius, Lithuania
LT303
🇱🇹Kaunas, Lithuania
PL301
🇵🇱Bialystok, Poland
PL308
🇵🇱Gdynia, Poland
PL304
🇵🇱Bydgoszcz, Poland
PL007
🇵🇱Katowice, Poland
PL309
🇵🇱Krakow, Poland
PL303
🇵🇱Poznan, Poland
PL002
🇵🇱Szczecin, Poland
PL003
🇵🇱Warszawa, Poland
PT302
🇵🇹Coimbra, Portugal
ZA006
🇿🇦Cape Town, South Africa
ZA002
🇿🇦Rosebank, South Africa
ES006
🇪🇸Barcelona, Spain
ES004
🇪🇸Salamanca, Spain
ES002
🇪🇸San Vicente del Raspeig, Spain
ES003
🇪🇸Santiago de Compostela, Spain
TW301
🇨🇳Kaohsiung, Taiwan
TW302
🇨🇳Kaohsiung, Taiwan
TW303
🇨🇳Tainan, Taiwan
UA008
🇺🇦Dnipropetrovsk, Ukraine
GB305
🇬🇧Preston, United Kingdom
US019
🇺🇸Orlando, Florida, United States
US336
🇺🇸Winston-Salem, North Carolina, United States
US004
🇺🇸Milwaukee, Wisconsin, United States